It is the primary purpose of this project to study some of the pertinent factors which influence cell differentiation and malignant transformation, using techniques and approaches which range from the microscopic to the molecular level. Particular emphasis is given to those systems in which murine RNA tumor viruses or chemical carcinogens may be the transforming agent. A variety of mouse model systems are used, including methylcholanthrene-induced sarcomas, plasma cell tumors, mammary tumors, and neuroblastomas. Current projects include: 1) effects of interferon on methylcholanthrene-induced sarcomas of the BALB/c mouse with the aim of defining antitumor activity and relationship to immune response; 2) effects of long term interferon treatment on NIH 3T3 cells transfected with various ras(Ha) related oncogenes; 3) effects of interferon on the assembly and maturation of murine retroviruses with special emphasis on the study of mechanisms whereby virions are rendered non-infectious. Our results suggest that the major effects of interferon on chemically-induced sarcomas do not appear to be mediated through anticellular activity, but are related to the immune response in the host animal. A number of experiments confirm the necessity of functional T cells in order for interferon to exert its antitumor effect. A considerable body of our data indicates that interferon affects murine retroviruses during the late stages of virus assembly and release. Even though whole virions are formed there are aberrations in the particle release stage. Those particles which are released have a markedly reduced infectivity which appears to be related to a lack of gp70. Since there is no demonstrable reduction of membrane-associated gp70 in infected interferon-treated cells, it would seem that there is a failure of incorporation of this viral envelope glycoprotein at the virus assembly site.